Outer membrane protein F of Pseudomonas aeruginosa has
vaccine efficacy against
infection by P. aeruginosa as demonstrated in a variety of animal models. Through the use of synthetic
peptides, three surface-exposed
epitopes have been identified. These are called
peptides 9 (aa 261-274 in the mature F
protein, TDAYNQKLSERRAN), 10 (aa 305-318, NATAEGRAINRRVE), and 18 (aa 282-295, NEYGVEGGRVNAVG). Both the
peptide 9 and 10
epitopes are protective when administered as a
vaccine. In order to develop a
vaccine that is suitable for use in humans, including infants with
cystic fibrosis, the use of viral vector systems to present the protective
epitopes has been investigated. An 11-amino
acid portion of
epitope 10 (AEGRAINRRVE) was successfully inserted into the antigenic B site of the
hemagglutinin on the surface of influenza virus. This chimeric influenza virus protects against challenge with P. aeruginosa in the mouse model of chronic pulmonary
infection. Attempts to derive a chimeric influenza virus carrying
epitope 9 have been unsuccessful. A chimeric plant virus, cowpea mosaic virus (CPMV), with
epitopes 18 and 10 expressed in tandem on the large coat
protein subunit (CPMV-PAE5) was found to elicit
antibodies that reacted exclusively with the 10
epitope and not with
epitope 18. Use of this chimeric virus as a
vaccine afforded protection against challenge with P. aeruginosa in the mouse model of chronic pulmonary
infection. Chimeric CPMVs with a single
peptide containing
epitopes 9 and 18 expressed on either of the coat
proteins are in the process of being evaluated.
Epitope 9 was successfully expressed on the coat
protein of tobacco mosaic virus (TMV), and this chimeric virus is protective when used as a
vaccine in the mouse model of chronic pulmonary
infection. However, initial attempts to express
epitope 10 on the coat
protein of TMV have been unsuccessful. Efforts are continuing to construct chimeric viruses that express both the 9 and 10
epitopes in the same virus vector system. Ideally, the use of a
vaccine containing two
epitopes of
protein F is desirable in order to greatly reduce the likelihood of selecting a variant of P. aeruginosa that escapes protective
antibodies in immunized humans via a mutation in a single
epitope within
protein F. When the chimeric influenza virus containing
epitope 10 and the chimeric TMV containing
epitope 9 were given together as a
combined vaccine, the immunized mice produced
antibodies directed toward both
epitopes 9 and 10. The
combined vaccine afforded protection against challenge with P. aeruginosa in the chronic pulmonary
infection model at approximately the same level of efficacy as provided by the individual chimeric virus
vaccines. These results prove in principle that a combined chimeric
viral vaccine presenting both
epitopes 9 and 10 of
protein F has
vaccine potential warranting continued development into a
vaccine for use in humans.